We have previously shown that anti-Ig heavy chain-specific antibodies, when injected into mice from birth onward, can achieve severe panspecific or class-specific immunosuppression of normal B-cells and prevent the growth of certain malignant lymphoid cells, particularly those of myelomas. We have also recently demonstrated that these antibodies can suppress normal and malignant lymphoid cells of adult animals and are freely transmitted transplacentally in mice, producing offspring in which humoral immunosuppression is virtually absolute and permanent. I now propose to expand our examination of anti-Ig immunosuppression, primarily in prenatal and adult mice, to achieve two broad objectives. 1. Several experimental approaches are planned to help elucidate the basic mechanism by which anti-Ig heavy chain-specific antibodies actually achieve immunosuppression. A comparison of the suppressive qualities of anti-Ig antisera produced in several diverse species (mammalian, avian, and reptilian), together with the use of Fc-deficient antibody fragments, will help to evaluate the role of Fc-dependent mechanisms (complement-mediated cytotoxicity, opsonization, antibody-dependent cellular cytoxicity, etc.). Studies with mice first treated as adults have been designed to determine the extent to which B-cell clonal maturity affects susceptibility to suppression. The definitive model of prenatal (transplacentally initiated) treatment will be used to reevaluate the roles of IgA and IgC as targets for anti-Ig suppression. 2. Prenatal, neonatal, and adult suppressive protocols will all be used to continue development of several clinically oriented models involving B-cell function. Among the potentially more useful of these models are myeloma prevention (and/or treatment) and reaginic antibody (IgE) regulation. The continuing evaluation of the involvment of antibodies in helminth expulsion is also proposed.